The study of protein phosphorylation in brain is expected to provide information relating to receptor linked effector mechanisms. During the past year, a new phenomenon has been observed in our laboratory. We have shown that the brain specific protein, S-100, is able to inhibit the phosphorylation of several synaptic proteins in a calcium dependent manner. The proteins characterized have molecular weights of 73, 56, 50 and 47 K. The 73 K protein is the most potently effected by S-100 and has been designated the S-100 mediated phosphoprotein or SMP. It is an acidic protein having an isoelectric point of 4.3, and efforts are underway to purify it from brain. The SMP is specific to brain and enriched in gray matter. The S-100 protein, therefore, appears to be a brain specific calmodulin-type protein with a reciprocal action to that of calmodulin. In other studies, an increased phosphorylation of a 45 K phosphoprotein has also been demonstrated in amygdala kindled animals. Phosphorylation of the 45 K protein is only increased in the amygdala of animals displaying kindled seizures. Animals exposed to ECS seizures or prekindled animals not displaying major motor seizures do not show increased phosphorylation of this protein. The 45 K protein may be involved in the behavioral sensitization process involved in kindling.